Does adenosine protect the heart by acting on the sarcoplasmic reticulum?

Mubagwa, Kanigula

doi:10.1016/s0008-6363(01)00550-8

Cited by 10 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy (induced by starvation or rapamycin) is dependent upon on the release of calcium from the sarco-endoplasmic reticulum (S/ER) [25] as is adenosine preconditioning [26]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA

et al. 2009

View full text Add to dashboard Cite

We have shown that the cellular process of macroautophagy plays a protective role in HL-1 cardiomyocytes subjected to simulated ischemia/reperfusion (sI/ R) (Hamacher-Brady et al. in J Biol Chem 281(40):29776-29787). Since the nucleoside adenosine has been shown to mimic both early and late phase ischemic preconditioning, a potent cardioprotective phenomenon, the purpose of this study was to determine the effect of adenosine on autophagosome formation. Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes. We investigated the effect of adenosine receptor agonists on autophagy and cell survival following sI/R in GFP-LC3 infected HL-1 cells and neonatal rat cardiomyocytes. The A 1 adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) (100 nM) caused an increase in the number of autophagosomes within 10 min of treatment; the effect persisted for at least 300 min. A significant inhibition of autophagy and loss of protection against sI/R measured by release of lactate dehydrogenase (LDH), was demonstrated in CCPA-pretreated cells treated with an A 1 receptor antagonist, a phospholipase C inhibitor, or an intracellular Ca(?2) chelator. To determine whether autophagy was required for the protective effect of CCPA, autophagy was blocked with a dominant negative inhibitor (Atg5 K130R ) delivered by transient transfection (in HL-1 cells) or protein transduction (in adult rat cardiomyocytes). CCPA attenuated LDH release after sI/R, but protection was lost when autophagy was blocked. To assess autophagy in vivo, transgenic mice expressing the red fluorescent autophagy marker mCherry-LC3 under the control of the alpha myosin heavy chain promoter were treated with CCPA 1 mg/kg i.p. Fluorescence microscopy of cryosections taken from the left ventricle 30 min after CCPA injection revealed a large increase in the number of mCherry-LC3-labeled structures, indicating the induction of autophagy by CCPA in vivo. Taken together, these results indicate that autophagy plays an important role in mediating the cardioprotective effects conferred by adenosine pretreatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA

et al. 2009

View full text Add to dashboard Cite

show abstract

“…19,[34][35][36] More recently, adenosine A1 receptor activation has been linked to new cardioprotective targets including the mitochondria [36][37][38] and sarcoplasmic reticulum. 39 A1 receptor activation is also implicated in adenosine's ability to blunt the stimulatory effects of catecholamines and inhibition of norepinephrine release from nerve terminals. 15 3.…”

Section: Discussionmentioning

confidence: 99%

Adenosine and lidocaine: a new concept in nondepolarizing surgical myocardial arrest, protection, and preservation

Dobson

Jones

2004

The Journal of Thoracic and Cardiovascular Surgery

100

114

View full text Add to dashboard Cite

show abstract

“…Adenosine may also stabilize myocardial excitability by activating the A 1 receptor subtype (and perhaps A 3 ), blunt the stimulatory effects of catecholamines (inhibiting sarcolemmal Na ϩ /H ϩ and Na ϩ / Ca 2ϩ exchangers), and inhibit norepinephrine release from nerve terminals (15,18). These electrophysiological and receptor-linked effects may have "downstream" metabolic effects leading to reduced Na ϩ and Ca 2ϩ entry via channels and exchangers (39,58,61) and improved handling of these cations by the sarcoplasmic reticulum (41) and mitochondria (17).…”

Section: Discussionmentioning

confidence: 99%

“…It should be added, however, that the involvement of sarcolemmal K ATP channels in early myocardial ischemia arose from studies using the nonspecific blocker glibenclamide (17,28) and the highly selective sarcolemmal K ATP blocker HMR-1,883 (6), but much controversy remains (17). Other potential sites of Adeno's actions, and perhaps Lido's actions, include the mitochondria (17,46) and sarcoplasmic reticulum (41).…”

Section: Discussionmentioning

confidence: 99%

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

Canyon

Dobson

2004

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), ventricular tachycardia (VT), or cardiac ischemia that show a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common antiarrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats (n = 49) were anesthetized with pentobarbital sodium (60 mg.ml(-1).kg(-1) i.p.) and instrumented for regional coronary occlusion (30 min) and reperfusion (120 min). Heart rate, blood pressure, and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 min before ischemia and extended throughout ischemia, terminating at the start of reperfusion. After 120 min, hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls (n = 12), 50% of adenosine only (305 microg.kg(-1).min(-1), n = 8), 0% in lidocaine only (608 microg.kg(-1).min(-1), n = 8), and 0% in AL at any dose (152, 305, or 407 microg.kg(-1).min(-1) adenosine plus 608 microg.kg(-1).min(-1) lidocaine, n = 7, 8, and 6). VT occurred in 100% of saline controls (18 +/- 9 episodes), 50% of adenosine-only (11 +/- 7 episodes), 83% of lidocaine-only (23 +/- 11 episodes), 60% of low-dose AL (2 +/- 1 episodes, P < 0.05), 57% of mid-dose AL (2 +/- 1 episodes, P < 0.05), and 67% of high-dose AL rats (6 +/- 3 episodes). VF occurred in 75% of saline controls (4 +/- 3 episodes), 100% of adenosine-only-treated rats (3 +/- 2 episodes), and 33% lidocaine-only-treated rats (2 +/- 1 episodes) of the rats tested. There was no deaths and no VF in the low- and mid-dose AL-treated rats during ischemia, and only one high-dose AL-treated rat experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats but only reached significance with the mid-dose treatment (saline controls 61 +/- 5% vs. 38 +/- 6%, P < 0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window in ischemic and nonischemic regions of the heart.

show abstract

Does adenosine protect the heart by acting on the sarcoplasmic reticulum?

Cited by 10 publications

References 18 publications

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA

Adenosine and lidocaine: a new concept in nondepolarizing surgical myocardial arrest, protection, and preservation

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat

Contact Info

Product

Resources

About